Injection Of Streptozocin Research Articles

Limb regeneration is impaired in an adult zebrafish model of diabetes mellitus

The zebrafish (Danio rerio) is an established model organism for the study of developmental processes, human disease, and tissue regeneration. We report that limb regeneration is severely impaired in our newly developed adult zebrafish model of type I diabetes mellitus. Intraperitoneal streptozocin injection of adult, wild-type zebrafish results in a sustained hyperglycemic state as determined by elevated fasting blood glucose values and increased glycation of serum protein. Serum insulin levels are also decreased and pancreas immunohistochemisty revealed a decreased amount of insulin signal in hyperglycemic fish. Additionally, the diabetic complications of retinal thinning and glomerular basement membrane thickening (early signs of retinopathy and nephropathy) resulting from the hyperglycemic state were evident in streptozocin-injected fish at 3 weeks. Most significantly, limb regeneration, following caudal fin amputation, is severely impaired in diabetic zebrafish and nonspecific toxic effects outside the pancreas were not found to contribute to impaired limb regeneration. This experimental system using adult zebrafish facilitates a broad spectrum of genetic and molecular approaches to study regeneration in the diabetic background.

Asiatic acid preserves beta cell mass and mitigates hyperglycemia in streptozocin‐induced diabetic rats

Type 1 diabetes is a chronic condition in which the pancreas produces little or no insulin due to the loss or dysfunction of pancreatic beta cells. This study investigated the beneficial effects of asiatic acid-a triterpenoid compound-preserved beta mass and mitigated hyperglycemia in streptozocin-induced diabetic rats. Diabetes mellitus was induced in adult male Wistar rats by a single intraperitoneal injection of streptozocin (60 mg/kg body weight). The diabetic rats were divided into untreated and asiatic acid (25 mg/kg) groups. Controls were intraperitoneal injection with citrate buffer. Blood glucose level, plasma insulin, and pancreas immunohistochemistry analysis were examined after a 2-week experimental period. AKT and Bcl-xL expression in the pancreatic islets of rats were evaluated by Western blot methods. Blood glucose levels were significantly reduced in rats receiving asiatic acid after streptozocin administration. Asiatic acid concomitantly increased serum insulin levels in diabetic rats. Immunohistochemical staining revealed a marked preservation by asiatic acid of insulin-producing beta cells in the pancreatic islets of the diabetic rats. Furthermore, asiatic acid in vivo induced pro-survival Akt kinase activation and Bcl-xL expression in the pancreatic islets of diabetic rats. These results suggest that asiatic acid exerts its glucose-lowering effects, in part through influences on beta-cell mass. Asiatic acid administration resulted in preservation and restoration of beta-cell mass and function in diabetic rodent models.

Long-term but Not Short-term Aspirin Treatment Attenuates Diabetes-associated Learning and Memory Decline in Mice

Increasing studies have shown that the patients with diabetes mellitus have an increased risk of cognitive impairment, dementia, and neurodegeneration. The present study was designed to evaluate the effect of aspirin on diabetes-associated learning and memory decline in mice. Diabetes was induced by a single intraperitoneal injection of streptozocin (150 mg/kg body weight) in C57BL/6 mice. The mice were administered with aspirin at a dose of 30 mg/kg by intragastric administration once a day for 1, 4 or 8 weeks respectively. 8 weeks after aspirin or vehicle treatment, the effect of aspirin on diabetes-associated learning and memory decline in mice was investigated by evaluating the mean escape latency and the percentage of time spent in target quadrant. The TNF-α, IL-1β contents, and acetylcholinesterase activity in hippocampus were assayed as well. The results showed that administration with aspirin for 4 weeks or 8 weeks significantly reduced the mean escape latency, the acetylcholinesterase activity, the TNF-α, IL-1β levels and increased the percentage of time spent in target quadrant. However, treatment with aspirin for 1 week did not ameliorate diabetes-associated learning and memory decline. The present study demonstrated that long-term aspirin treatment attenuates diabetes-associated learning and memory decline in mice, and that the effect of aspirin was related to its anti-inflammatory potency.

Production of a Type 2 Maternal Diabetes Rodent Model Using the Combination of High-Fat Diet and Moderate Dose of Streptozocin

Introduction. Pregnancy may be complicated by maternal diabetes. The following experiments were performed in an attempt to produce mouse models of insulin-resistant maternal diabetes. Methods. CD1 females received 200 mg/kg streptozocin (STZ) to model insulin-dependent diabetes (T1 group). Another group of females (T2 group) was put on a HFD 4 weeks before receiving 100 mg/kg STZ. After 4 additional weeks of HFD, hyperglycemic females were separated and bred. In another experiement, CD1 females were fed a HFD for 4 weeks before receiving an intravenous (GDM1 group) or intraperitoneal (GDM2 group) injection of 100 mg/kg STZ. Females from GDM2 group were bred at the same day of the STZ injection. Females from GDM1 group were bred 4 weeks after the STZ injection. Results and Conclusion. About 25% of the females from T2 group became hyperglycemic after 4 weeks of the injection of STZ. Fifty percent of the females from GDM1 group reached hyperglycemic levels greater than 250 mg/dl during pregnancy. The combination of HFD and moderate STZ in CD1 mice therefore produced hyperglycemic females; however numbers of these mice were somewhat low.

Antidiabetic effect of a new peptide from Squalus mitsukurii liver (S-8300) in streptozocin-induced diabetic mice

We have evaluated the antidiabetic effect of S-8300 (a peptide extracted from shark liver (Squalus mitsukurii)) in streptozocin (streptozotocin)-diabetic mice. Diabetes was induced by a single intravenous injection of streptozocin (150 mg kg(-1)). The effects of S-8300 (3 or 10 mg kg(-1)) on diabetic mice were investigated by observing the changes in the levels of fasting plasma glucose, glycosylated haemoglobin, hepatic glycogen, triglycerides, cholesterol, free fatty acid, superoxide dismutase, and malondialdehyde. Body weight, kidney weight and the degree of injured beta-cells in pancreatic islets were recorded also. Diabetic mice treated with S-8300 showed a significant decrease in the levels of fasting plasma glucose, glycosylated haemoglobin, triglycerides, cholesterol, free fatty acid in plasma and malondialdehyde in tissues. The animals showed a significant increase in the content of hepatic glycogen and the activity of superoxide dismutase. Treatment with S-8300 attenuated the degree of injured beta-cells in the pancreatic islets. The effect of S-8300 was similar to that of glibenclamide (5 mg kg(-1)).

Antidiabetic Effects of Total Flavonoids from Litsea Coreana leve on Fat-Fed, Streptozotocin-Induced Type 2 Diabetic Rats

This study was initiated to determine the possible antidiabetic effects of total flavonoids of Litsea Coreana leve (TFLC), an alcohol extract from the dried leaves of Litsea Coreana leve, on type 2 diabetic rats. Male Sprague-Dawley rats (n = 40, 160-180 g) were divided into two groups and fed with normal chow diet (Normal Control group) or high-fat diet (HFD) for a period of 4 weeks. After 4 weeks of dietary manipulation, the HFD-fed rats were injected with 30 mg/kg streptozocin (STZ) to induce diabetes 72 hours after STZ injection. These diabetic rats were randomly divided into 3 groups (n = 10): Diabetic Control group, Diabetic + TFLC group and Diabetic + PIO group. Diabetic + TFLC group and Diabetic + PIO group were orally administered with 400 mg/kg TFLC or 10 mg/kg pioglitazone (all suspended in 0.5% CMC-Na) respectively for 6 weeks. All rats were examined for body weight, serum and hepatic biochemical indices, content of malondialdehyde (MDA), activities of superoxide dismutase (SOD) and pathological changes in liver and pancreas, as well as protein tyrosine phosphatase 1B (PTP1B) expression in liver. The diabetic rats became obese, insulin resistant, hyperglycemic and hyperlipidemic. Treatment with TFLC showed a significant increase in insulin sensitivity, serum HDL-C level and SOD activities, meanwhile marked decrease in body weight, serum FFA, TC, TG, LDL-C, CRP, MDA content. TFLC also attenuated pathologic alterations in liver and pancreatic islet. Furthermore, TFLC was found to decrease the expression of PTP1B in diabetic rat liver. These results suggested that TFLC could ameliorate hyperglycemia, hyperlipoidemia, inflammation and oxidation stress, as well as insulin resistance of type 2 diabetic rats.

Usefulness of Mitral Annulus Velocity for the Early Detection of Left Ventricular Dysfunction in a Rat Model of Diabetic Cardiomyopathy

Diabetic cardiomyopathy (DMCMP) is characterized by myocardial dysfunction regardless of coronary artery disease in diabetic patients. The features of LV dysfunction in rat model of type 1 DM induced by streptozocin, are variable and controversial. Thus, we tested the usefulness of tissue Doppler imaging in the early detection of ventricular dysfunction in a rat model of DMCMP. Diabetes was induced by intra-peritoneal injection of streptozocin (70 mg/kg) in 8 weeks of Sprague-Dawley rat. Diagnosis of diabetes was defined as venous glucose level over 350 mg/dL 48 hrs after streptozocin injection. Echocardiography was done at baseline and 10 weeks after diabetes induction both in diabetes group (n=15) and normal control (n=10). After echocardiography at 10 weeks, invasive hemodynamic measurement using miniaturized conductance catheter was done in both groups. Ten weeks after diabetes induction, heart and lung mass indexes of diabetes were larger than those of normal control (3.2+/-0.3 vs. 2.4+/-0.2 mg/g, p<0.001, 5.5+/-1.1 vs. 3.6+/-0.6 mg/g, p<0.001, respectively). In echocardiographic data, s' (2.4+/-0.4 vs. 3.1+/-0.5 cm/s, p<0.001), e' velocity of mitral annulus (2.9+/-0.6 vs. 3.8+/-1.1 cm/s, p<0.001), and E/e' ratio (27.1+/-5.6 vs. 19.7+/-2.6, p<0.001) were impaired in diabetes group. In hemodynamic measurement, there were no differences in ejection fraction, peak dP/dt between the diabetic group and normal control. However, load independent indexes of contractility, the slope of the end-systolic pressure volume relation (0.18+/-0.07 vs. 0.62+/-0.18 mmHg/microL, p<0.001) and preload recruitable stroke work (51.8+/-22.0 vs. 90.9+/-22.5 mmHg, p<0.001) were impaired in diabetic group compared to normal control. In a rat model of diabetic cardiomyopathy, tissue Doppler imaging of mitral annulus can be a good modality for early detection of myocardial dysfunction.

Myocardial Iron Metabolism in the Regulation of Cardiovascular Diseases in Rats

The iron homeostasis plays an important role in cardiac function. To understand how it acts in diabetic and ischemic myocardial injury, we studied the myocardial iron metabolism in diabetic and myocardial ischemic rats. Diabetic rats were induced by intraperitoneal injection of streptozocin (STZ) after intragastric administration of a high-fat diet while the ischemic rat hearts were subjected to coronary artery ligation for 0.5, 1, 6, 12 or 24 h, respectively. In STZ-induced diabetic rats, the contents of serum and myocardial iron were found elevated obviously accompany with the decrease of hepatic iron determined by the flame emission atomic absorption spectroscopy. The levels of superoxide dismutase (SOD), malonaldehyde (MDA) and serum ferritin were increased in diabetic rats. Moreover, protein level of divalent metal transporter 1 (DMT1) was decreased while that for transferrin receptor (TfR) and metal transporter protein 1 (MTP1) was increased. In contrast, no alteration of iron concentration was observed in the ischemic rats. The expression of DMT1, TfR and MTP1 has not changed after infraction. The findings suggested that diabetes mellitus (DM) induced the iron overload in the myocardium, at least in part by up-regulation of TfR. Meanwhile, down-regulation of DMT1 and up-regulation of MTP1 were induced to alleviate the excessive iron in the myocardium. However, myocardial infraction (MI) has not broken the balance of myocardial iron. In conclusion, the iron homeostasis reacts differently in DM and MI.

ATP-sensitive potassium channels contribute to the time-dependent alteration in the pentylenetetrazole-induced seizure threshold in diabetic mice

Although there is evidence that diabetes affects seizure susceptibility, the underlying mechanism has not been completely understood. Several studies also suggest a pivotal role for K ATP channels in the seizure modulation. The aim of the present study was to evaluate the seizure threshold induced by pentylenetetrazole in diabetic mice at different times (3 days, 1–8 weeks) after induction of diabetes with streptozocin and to examine the possible role of ATP-sensitive potassium (K ATP) channels in this manner. Our data showed a time-dependent alteration in the threshold in diabetic mice, reaching a peak on week 2 after streptozocin injection and declining significantly afterwards. The seizure threshold in 8-week diabetic mice was even lower than control levels, though the difference was not significant. The K ATP channel opener cromakalim (0.1–30 μg/kg, i.p.) significantly increased the seizure threshold in control mice. Although the K ATP channel blocker glibenclamide (0.5, 1 mg/kg) had no effect, it prevented the effects of the potent dose of cromakalim (30 μg/kg) on seizure threshold in control mice. Glibenclamide (1 mg/kg, i.p.) also decreased the seizure threshold in 2-week diabetic mice to the control levels which was blocked by pre-treatment with cromakalim (10 μg/kg, i.p.). Cromakalim (10 μg/kg, i.p.) significantly increased the seizure threshold in 8-week diabetic mice which was inhibited by pre-treatment with glibenclamide (1 mg/kg, i.p.). We demonstrated a time-dependent alteration in the pentylenetetrazole-induced seizure threshold in diabetic mice. This phenomenon might be due to the probable alteration in the K ATP channel functioning during the diabetic condition.

In vivo silencing of the CaV3.2 T-type calcium channels in sensory neurons alleviates hyperalgesia in rats with streptozocin-induced diabetic neuropathy

Earlier, we showed that streptozocin (STZ)-induced type 1 diabetes in rats leads to the development of painful peripheral diabetic neuropathy (PDN) manifested as thermal hyperalgesia and mechanical allodynia accompanied by significant enhancement of T-type calcium currents (T-currents) and cellular excitability in medium-sized dorsal root ganglion (DRG) neurons. Here, we studied the in vivo and in vitro effects of gene-silencing therapy specific for the CaV3.2 isoform of T-channels, on thermal and mechanical hypersensitivities, and T-current expression in small- and medium-sized DRG neurons of STZ-treated rats. We found that silencing of the T-channel CaV3.2 isoform using antisense oligonucleotides, had a profound and selective anti-hyperalgesic effect in diabetic rats and is accompanied by significant down-regulation of T-currents in DRG neurons. Anti-hyperalgesic effects of CaV3.2 antisense oligonucleotides in diabetic rats were similar in models of rapid and slow onset of hyperglycemia following intravenous and intraperitoneal injections of STZ, respectively. Furthermore, treatments of diabetic rats with daily insulin injections reversed T-current alterations in DRG neurons in parallel with reversal of thermal and mechanical hypersensitivities in vivo. This confirms that CaV3.2 T-channels, important signal amplifiers in peripheral sensory neurons, may contribute to the cellular hyperexcitability that ultimately leads to the development of painful PDN.

In-vivo antidiabetic effect of Cistus laurifolius L. leaves

The genus Cistus (Cistaceae) is one of the characteristic genera of the Mediterranean region, colonizing degraded areas [1]. In Turkish folk medicine, various parts of Cistus laurifolius L. are used to treat peptic ulcer and various types of pains, i.e., rheumatic, back pain, etc. It has been used for the treatment of stomach ache and gastric ulcer in the folk medicine since the time of Dioscorides, i.e., for at least 2000 years in Anatolia. The tea prepared from the leaves is used to decrease symptoms of diabetes hypoglycemic [2,3]. In the present study, the hypoglycemic and antihyperglycemic effects of water and ethanol extracts of C. laurifolius were evaluated by using in vivo methods in normal, glucose loaded hyperglycemic and streptozocin-induced diabetic rats. Diabetes was induced by intraperitoneal injection of streptozocin at the dose of 55mg/kg. Blood glucose levels of animals were measured by the glucose oxidase method. Tolbutamide (100mg/kg) was used as reference drug. All data were compared to control group.

Effect of crocin on the progression and treatment of diabetic neuropathy in mice

Oxidative stress is a mechanism which has been implicated to play a major role in pathogenesis of diabetic neuropathy. Antioxidant agents have an important place in prevention and treatment of diabetic neuropathy. In previous studies, the antioxidant effects of saffron and two active constituents (crocin and safranal) have been reported [1]. Thus, in this study, the effects of crocin on diabetic hyperalgesia are investigated in mice. Diabetes was induced by single injection of streptozocin (200mg/kg).Three doses of crocin (50, 100 and 200mg/kg/day) were administered subcutaneously in three groups of normal and diabetic animal for one or four weeks or in single administration. Hyperalgesia was evaluated using tail flick test. Four weeks of treatment with doses of 100 and 200mg/kg/day of crocin prevented the induction of hyperalgesia (from 44 to 52%) in diabetic mice (P&lt;0.05 and P&lt;0.01, respectively). Also after induction of hyperalgesia, the treatment of diabetic mice by administration of crocin (50, 100 and 200mg/kg/day) for one week (P&lt;0.05) or single dose (P&lt;0.001) was effective to prevent the induction of hyperalgesia (up to 50%). It can be concluded that the crocin is effective in prevention and treatment of hyperalgesia in diabetic mice.

Immnoprecipitation of Gastric H+/K+ATPase Beta Subunit in Hyperglycemic Mice

An upregulation of gastric H+/K+ATPase has been observed in kidney epithelial cells with higher glucose medium. It also has been reported that gastric H+/K+ATPase (HKA) associates with type 1 diabetic patients. We examined the gastric HKA beta subunit protein levels in the isolated kidney medulla (OMCD) in streptozocin‐induced diabetic mice. Hyperglycemia was induced by intraperitoneal injections of streptozocin (50mg/kg) and monitored for 5 days. The mouse kidney medulla was dissected and lysed with a lysis buffer (pH 8). Cell lysate was incubated with monoclonal antibody (HKA beta subunit, 34 kDa) overnight under agitation at 4 °C. After incubation, protein A agarose macrobeads (85 μL) were added to the cell lysate and the lysate/bead mixture was incubated at 4 °C. Beads were washed with lysis buffer to remove protein. The amount of HKA beta subunit was quantified by Bradford protein assay. Serum glucose was 160 ± 25.78 mg/dL in normal mice and was 475 ± 60.90 mg/dL in the hyperglycemic group. At a wavelength of 540 nm, the HKA beta subunit protein absorbance was 0.056 ± 0.019 (n=16) in normal mice. In hyperglycemic mice, the HKA beta subunit absorbance was 0.070 ± 0.024 (n=28, p=0.05). The increased absorbance of gastric H+/K+ATPase beta subunit protein in hyperglycemic mice suggests that hyperglycemia stimulates the production of gastric H+/K+ATPase in the mouse kidney.

Effect of propentofylline on activation of astrocytes in spinal cord in a rat model of diabetic neuropathic pain

Objective To investigate the effect of propentofylline on activation of astrecytes in the spinal cord in a rat model of diabetic neuropathic pain(DNP).Methods Pathogen-free SD rats of both sexes aged 2 months weighing 180-200 g were used in this study.Diabetes was induced by intraperitoneal(IP)1% streptozocin(STZ)60 mg/kg.Blood glucose level was measured before(T1)and at 2,7,14,21,28,35 days after IP STZ injection(T2-7).Diabetes Was confirmed by blood glucose level>16.7 mmol/L.Paw withdrawal threshold to von Frey filament stimulation(PWT)Was measured at T1,T3-7.Induction of neuropathic pain WaS considered successful in ccessful in animals with PWT reduced by more than 50%of the baseline.Twenty animals in which DNP was successfully induced were randomly divided into 2 groups(n=10 each):groupⅠdiabetes meatus(DM)and groupⅡ pmpentofylline(PP).Another 10 age-matched normal rats served as control group(Nc),Grorp PP received IP propentofylline 10 ms/kg once B day for 7 consecutive days starting from T6.The animals were killed at T2 and the lumbar segment of the spinal cord Was removed for determination of glial fibrillary acidic protein(GFAP)in the astmcytes in the spinal cord by immuno-histochemical assay.Results PWT Was aignitlcantly lower at T4-7 in group DM and PP than in control group(NC)and Was significantly higher at T7 in group PP than in group DM.Immuno-himochemical assay showed that GFAP-positive astrocytes in the dorsal hom of the spinal cord was significantly increased in diabetic rats and pmpentofyUine significantly attenuated the increase.Conclusion Inhibition of astwcytes in the spinal cord is involved.m attenuation of diabetic neuropathic pmn by propentofylline. Key words: lndoles; Diabetic neuropathy; Neuralgia; Spinal cord; Astwcytes

Aortic stiffness in diabetes mellitus – association with glutamine and heat shock protein 70 expression: a pilot study based on an experimental rodent model

Background: Diabetes mellitus (DM) alters arterial wall compliance and causes aortic stiffness, which is a predictor of vascular mortality. Heat shock proteins (HSPs) are involved in the protection of cells under stress. We evaluated aortic stiffness in DM and the effects of glutamine (which induces HSP 70) on HSP 70 levels in experimental DM. Materials and methods: Male Sprague-Dawley rats (n = 30) were divided into three groups: Control (Group 1), DM (Group 2) and glutamine-treated DM (Group 3). DM was induced using streptozocin injection. Group 3 rats received two doses of glutamine during the fourth week. Blood and infrarenal aortic tissue samples were obtained for analysis at the end of the fourth week. Results: Compared with Group 1, serum HSP 70 levels were significantly increased in Groups 2 and 3. Aortic HSP 70 was increased in DM. There was a significant difference in aortic HSP 70 with glutamine injection (Group 1 versus Group 3). DM also interfered with the elastin content of the aorta. There was a significant correlation between the serum glucose and serum and aortic HSP 70 levels and between serum and aortic HSP 70 levels; as well as between severity of DM and aortic elastin levels. Conclusions: DM causes aortic stiffness and this may contribute to the increase in mortality and morbidity associated with DM. The expression of HSP 70 may become a therapeutic target.

Danisco invests in second-generation bioethanol project with DuPont

Dulaglutide, a novel long-acting glucagon-like peptide 1 (GLP-1) receptor agonist, is an incretin mimetic approved for type 2 diabetes mellitus (T2DM) treatment. Alzheimer's disease (AD) is called type 3 diabetes. The aim of this study is to explore the effects of dulaglutide on the learning and memory impairment in AD mice induced by injection of streptozocin (STZ) via intracerebroventricularly (i.c.v.). 32 male C57/BL6 mice were randomly divided into four groups: control group (CON); AD model group (STZ); dulaglutide treated (Dul); dulaglutide and exendin(9–39) (Ex). Western blotting was used to detect the levels of phosphorylated tau, neurofilament (NFs) proteins and phosphorylated PI3K/AKT/GSK3β signaling pathway. Morris water maze (MWM) test was used to assess the spatial learning and memory ability. The results displayed that the hyperphosphorylation of tau and NFs were increased in the STZ and Ex groups compared to the control and Dul groups. Dulaglutide also significantly shortened the escape latency and increased the number of hidden platform crossings in MWM test. The effects of dulaglutide on decreasing the hyperphosphorylation of tau and NFs proteins through improving the PI3K/AKT/GSK3β signaling pathway may be related to its protective effects on impairment of AD-like learning and memory.

Anatomical versus functional β‐cell mass in experimental diabetes

The ability of pancreatic beta-cell mass to vary according to insulin requirements is an important component of optimal long-term control of glucose homeostasis. It is generally assumed that alteration of this property largely contributes to the impairment of insulin secretion in type 2 diabetes. However, data in humans are scarce and it is impossible to correlate beta-cell mass and function with the various stages of the disease. Thus, the importance of animal models is obvious. In rodents, increased beta-cell mass associated with an increase in the function of individual beta-cells contributes to the adaptation of the insulin response to insulin resistance in late pregnancy and in obesity. A reduction in beta-cell mass always corresponds to an alteration in insulin secretory capacity of islet tissue (Zucker diabetic fatty and Goto-Kakisaki rats, db/db mice). During regenerative processes following experimental reduction of beta-cell mass [partial pancreatectomy, streptozocin (STZ) injection], beta-cell mass increase is not associated with a corresponding improvement of beta-cell function, thus indicating that regenerative beta-cells did not achieve functional maturity. The main lesson from experimental diabetes is therefore that beta-cell mass cannot always predict functional capacity of the beta-cell tissue and that the functional beta-cell mass rather than the anatomical beta-cell mass must be taken into account at all times.

Effects of lisinopril on diabetic peripheral neuropathy: experiment with rats

To investigate the effects of lisinopril, an angiotensin-converting enzyme inhibitor, on diabetic peripheral neuropathy (DNP). Twenty-five Wistar rats underwent intravenous injection of streptozocin to establish diabetes models and 10 rats were injected with sodium citrate solution as normal controls. The diabetic rats were randomly divided into 2 groups: lisinopril group treated with gastric perfusion of lisinopril daily for 8 weeks, and diabetic control group. The diabetic controls and normal controls were treated with gastric perfusion of water. Sciatic nerve electrode penetration method was used to measure the motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV). Light and heat pain measuring apparatus was used to measure the pain threshold. Then the sciatic nerves were isolated. Electron microscopy was used to observe the ultra-structure. The contents of superoxide dismutase (SOD) and malonyldialdehyde (MDA), and Na(+)K(+)-ATPase activity were detected by chemical colorimetry. Immunohistochemistry was used to detect the CD34 in the sciatic nerve. The capillary density of sciatic nerve was calculated. The MNCV and SNCV levels of the lisinopril group were both lower than those of the 2 control groups (all P < 0.01). The potency of heat pain leg retraction response of the lisinopril group was significantly shorter than that pf the diabetic control group (P < 0.05). The pathological changes of the lisinopril group were milder than those of the other groups. The SOD level and the Na(+)K(+)-ATPase activity of the diabetic group were significantly lower than those of the normal control group, and the MDA of the diabetic group was significantly higher than those of the other 2 groups (all P < 0.05). And the SOD level and Na(+)K(+)-ATPase activity of the lisinopril group were significantly higher than those of the diabetic control group, and the MDA level of the lisinopril group was significantly lower than that of the diabetic control group. The capillary density of sciatic nerve of the diabetic control group was lower and the normal control group, and that of the lisinopril group was significantly higher than that of the diabetic control group (P < 0.01). ACE inhibitors effectively prevent and treat DPN.

Taurine rescues vascular endothelial dysfunction in streptozocin-induced diabetic rats: Correlated with downregulation of LOX-1 and ICAM-1 expression on aortas

Macroangiopathy is a major complication of diabetes mellitus in which dysfunction of vascular endothelium induced by excessive oxidative stress is an early and key determinant. As an endogenous antioxidant, taurine possesses endothelial protective effect in vitro. LOX-1 is an endothelial receptor for oxidized low-density lipoprotein (oxLDL) which might mediate endothelial dysfunction and subsequent atherogenesis in diabetes. We used streptozotocin-induced rats as models of type 1 diabetes to evaluate the protective effect of taurine against vascular endothelial dysfunction in type 1 diabetes and the possibly involved molecule mechanism. Eight male Wistar rats were used as normal control group. Sixteen diabetic rats induced by one single injection of streptozocin (60 mg/kg, i.p.) were randomly divided into two groups after the diabetes onset: diabetes mellitus group and taurine-treated diabetes group. 6 weeks afterward, endothelium-dependent vasodilation of isolated thoracic aorta, serum oxLDL and soluble intercellular adhesion molecule (sICAM-l) levels, LOX-1 and intercellular adhesion molecule (ICAM-1) expression on aortas were determined respectively. Streptozocin-induced diabetic rats were complicated with excessive oxidative stress and endothelial dysfunction: increased serum oxLDL and sICAM-1, inhibited endothelium-dependent vasodilator responses to acetylcholine (1 nM–0.1 μM). Simultaneously, LOX-1 and ICAM-1 expression were enhanced in aortas of diabetic rats; whereas blunted endothelium-dependent vasodilator responses to acetylcholine, increased serum oxLDL and sICAM-1 level as well as overexpression of LOX-1 and ICAM-1 were all attenuated significantly by taurine treatment. In conclusion, taurine improves vascular endothelial dysfunction induced by experimental type 1 diabetes and this effect might be associated with downregulation of LOX-1 and ICAM-1 expression on aortic vascular endothelium via its antioxidative property.

Streptozocin-Induced Diabetic Mouse Model of Urinary Tract Infection

Diabetics have a higher incidence of urinary tract infection (UTI), are infected with a broader range of uropathogens, and more commonly develop serious UTI sequelae than nondiabetics. To better study UTI in the diabetic host, we created and characterized a murine model of diabetic UTI using the pancreatic islet beta-cell toxin streptozocin in C3H/HeN, C3H/HeJ, and C57BL/6 mouse backgrounds. Intraperitoneal injections of streptozocin were used to initiate diabetes in healthy mouse backgrounds, as defined by consecutive blood glucose levels of >250 mg/dl. UTIs caused by uropathogenic Escherichia coli (UTI89), Klebsiella pneumoniae (TOP52 1721), and Enterococcus faecalis (0852) were studied, and diabetic mice were found to be considerably more susceptible to infection. All three uropathogens produced significantly higher bladder and kidney titers than buffer-treated controls. Uropathogens did not have as large an advantage in the Toll-like receptor 4-defective C3H/HeJ diabetic mouse, arguing that the dramatic increase in colonization seen in C3H/HeN diabetic mice may partially be due to diabetic-induced defects in innate immunity. Competition experiments demonstrated that E. coli had a significant advantage over K. pneumoniae in the bladders of healthy mice and less of an advantage in diabetic bladders. In the kidneys, K. pneumoniae outcompeted E. coli in healthy mice but in diabetic mice E. coli outcompeted K. pneumoniae and caused severe pyelonephritis. Diabetic kidneys contained renal tubules laden with communities of E. coli UTI89 bacteria within an extracellular-matrix material. Diabetic mice also had glucosuria, which may enhance bacterial replication in the urinary tract. These data support that this murine diabetic UTI model is consistent with known characteristics of human diabetic UTI and can provide a powerful tool for dissecting this infection in the multifactorial setting of diabetes.